We are studying the interaction of human lymphocytes bearing the Fc receptor with surfaces coated by antigen-antibody complexes. This interaction is a model for the binding of killer lymphocytes to antibody-coated target cells which leads to the death of the target cell. A morphological alteration in the lymphocytes associated with this interaction was found to be inhibited by drugs affecting energy metabolism, microtubules, microfilaments, and intracellular cAMP levels. There is an excellent quantitative correlation of the inhibition of these drugs of the visible flattening of these cells and the corresponding drug inhibition of the killing mediated by these cells. This implies that a similar flattening may be an important aspect of the killing process. An EM study showed, unexpectedly, that all of these cells bearing the Fc receptor contained bundles of macrotubules in their cytoplasm; several lines of evidence suggest that they are composed of tubulin and may play a role in uropod formation. The adhesion process in these cells is accompanied by a 4-5 fold increase in glucose oxidation to CO2 and in lactate production, while increases in protein and DNA synthesis do not occur.